P1.02-037 Mutations of EGFR and KRAS Genes in Belorussian Patients With Non-Small Cell Lung Cancer

Abstract

Mutations of the epidermal growth factor receptor (EGFR) cause increased activation of EGFR and sensitivity of patients with non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKIs). The effectiveness of TKIs also depends on mutations of the KRAS gene that encodes small GTPase that is activated in response to a signal from EGFR and transmits it to the cascade of tyrosine kinases. Treatment of patients with KRAS mutations by TKIs is inefficient. Therefore, the research of these alterations plays an important role in determining the possibility of additional factors prognosis of NSCLC and adjusting individual tumor therapy. The aim of this study is to identify mutations in the exons 19 and 21 EGFR gene and in the exon 2 KRAS gene in patients with NSCLC. Analysis of mutations in the EGFR and KRAS genes was performed by PCR followed by sequencing DNA, which was extracted from the tumor and non-tumor lung tissues and blood samples of 97 patients with NSCLC (71 men, 26 women). 51 people have an adenocarcinoma (AC) and 46 people - squamous cell carcinoma (SCC). Analysis of mutations in the EGFR gene showed that the frequency of classical mutations is 5,2% of deletions in exon 19 (p.E746_A750del and p.L747_P753>S) and 1,1% of p.L858R mutation in exon 21. All mutations were detected only in the tumor tissue of non-smoking women with AC. Thus, 27,3% of women with AK are carriers of mutations in EGFR gene. These types of mutations were not detected among men. Also in the researched group was identified silent mutation c.2508C>T in exon 21 in the tumor, non-tumor tissue and blood among 3,3% of patients. Analysis of mutations in exon 2 KRAS gene detected 3 types of mutations: p.G12D (1,03%), p.G12C (2,06%) и p.G13C (1,03%). The frequency of all mutations was 4,1% in the total group of patients. The mutations were found only in tumor tissues of men. 75% of mutations carriers are smokers. Analysis of KRAS gene mutations in association with the development of a specific histological type of lung cancer showed that mutations are more common in patients with AC (5,9%) than in patients with SCC (2,2%). Thus, in the researched group of patients mutations in the EGFR gene were found only among non-smoking women with AC, mutations in the EGFR gene were detected only among men independently of histological type of NSCLC.